High throughput mechanical property and bulge testing of materials libraries

ABSTRACT

A method for high throughput mechanical property and bulge testing of materials libraries. A plurality of samples on a substrate are monitored for their response to a force from a fluid.

TECHNICAL FIELD

The present invention generally relates to the field of materialscharacterization. In particular, the invention relates to highthroughput screens for evaluating mechanical or physical properties oflibraries of polymers or other materials.

BACKGROUND OF THE INVENTION

Currently, there is substantial research activity directed toward thediscovery and optimization of polymeric materials for a wide range ofapplications. Although the chemistry of many polymers and polymerizationreactions has been extensively studied, nonetheless, it is rarelypossible to predict a priori the physical or chemical properties aparticular polymeric material will possess or the precise compositionand architecture that will result from any particular synthesis scheme.Thus, characterization techniques to determine such properties are anessential part of the discovery process.

Combinatorial chemistry refers generally to methods for synthesizing acollection of chemically diverse materials and to methods for rapidlytesting or screening this collection of materials for desirableperformance characteristics and properties. Combinatorial chemistryapproaches have greatly improved the efficiency of discovery of usefulmaterials. For example, material scientists have developed and appliedcombinatorial chemistry approaches to discover a variety of novelmaterials, including for example, high temperature superconductors,magnetoresistors, phosphors and catalysts. See, for example, U.S. Pat.No. 5,776,359 (Schultz, et al). In comparison to traditional materialsscience research, combinatorial materials research can effectivelyevaluate much larger numbers of diverse compounds in a much shorterperiod of time. Although such high-throughput synthesis and screeningmethodologies are conceptually promising, substantial technicalchallenges exist for application thereof to specific research andcommercial goals.

The characterization of polymers or other materials using combinatorialmethods has only recently become known. Examples of such technology aredisclosed, for example, in commonly owned U.S. Pat. Nos. 6,182,499(McFarland, et al); 6,175,409 B1 (Nielsen, et al); 6,157,449 (Hajduk);6,151,123 (Nielsen); 6,034,775 (McFarland, et al); 5,959,297 (Weinberg,et al), all of which are hereby expressly incorporated by referenceherein.

Of particular interest to the present invention are combinatorialmethods and apparatuses for screening polymers and other materials forphysical or mechanical characteristics. Screening of the materials formechanical properties presents a multitude of challenges. As an example,conventional instruments, such as conventional stress or strain testingmachines and other apparatuses traditionally lack the ability to screenmechanical properties of several materials in rapid succession, inparallel, on a single substrate or a combination thereof. Thus,challenges are presented for forming systems that can quickly processand test (either in parallel or in serial succession) mechanicalproperties of many materials.

SUMMARY OF THE INVENTION

The present invention provides instruments and methods for screeningcombinatorial libraries that addresses many of the problems encounteredwhen using conventional instruments. For example, the disclosedinstruments can measure mechanical properties of library members inrapid serial or parallel test format, and can perform tests on smallamounts of material, which are easily prepared or dispensed usingart-disclosed liquid or solid handling techniques. Compared toconventional instruments, the disclosed instruments afford faster sampleloading and unloading, for example, through the use of disposablelibraries of material samples.

Thus, one aspect of the present invention provides instruments formeasuring mechanical properties of a combinatorial library of materials.The instruments include at least one mounting member to which thelibrary of material samples is removably secured for testing; at leastone source selected from the group consisting of a fluid, a voltage, apiezoelectric and a combination thereof for delivering one or moreforces to each library member; and at least one sensing device formonitoring the response each library member to the one or more forces.

Another aspect of the present invention provides methods of screening acombinatorial library of materials. In a preferred embodiment, themethods include providing a combinatorial library of materialscomprising at least four different samples, and delivering one or moreforces to at least two of the samples simultaneously by a sourceselected from the group consisting of a fluid, a voltage, apiezoelectric and a combination thereof. The methods further includemonitoring the response of each library member to the one or moreforces. In another preferred embodiment, the method includes providing acombinatorial library of materials having at least four differentsamples; delivering one or more force to each of the samples serially bya source selected from the group consisting of a fluid, a voltage, apiezoelectric and a combination thereof; and monitoring the response ofeach library member to the one or more forces at a throughput rate nogreater than about 10 minutes per sample. Depending on the type of forceapplied, the methods can screen libraries of materials for a variety ofmechanical properties related to Young's modulus (e.g., flexure,uniaxial extension, biaxial compression, and shear), failure (stress andstrain at failure, toughness), adhesion, or others.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a flowchart of possible steps for methods of the presentinvention.

FIG. 2A shows a block diagram of a potential platform system forexecuting methods and for operating systems of the present invention.

FIG. 2B shows a flowchart of the general steps for the methods of thepresent invention.

FIG. 3 shows a perspective view of one embodiment of a bulge testinstrument that can be used for high throughput mechanical propertyscreening.

FIG. 4 shows a perspective view of one embodiment of a vessel that canbe used in the bulge test instrument shown in FIG. 3.

FIG. 5 shows a perspective view of one embodiment of a substrate thatcan be used in the bulge test instrument.

FIG. 6 shows a perspective view of one embodiment of a capacitivepull-in instrument that can be used for high throughput mechanicalproperty screening.

FIG. 7 shows a perspective view of one embodiment of a piezoelectricinstrument that can be used for high throughput mechanical propertyscreening.

FIG. 8 shows a view of one end of an embodiment of a piezoelectricbender that can be used in the piezoelectric instrument shown in FIG. 7.

FIG. 9 shows a side view of one embodiment of a piezoelectric benderthat can be used in the piezoelectric instrument shown in FIG. 7.

FIG. 10 shows the response of the piezoelectric bender shown in FIG. 9when voltage is applied to it.

FIG. 11 shows a schematic view of one embodiment of a bulge testinstrument with an environmental chamber.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Glossary

The following terms are intended to have the following general meaningsas they are used herein.

1. Fluid: The term “fluid” refers to a gas or a liquid.

2. Mixture: The term “mixture” refers to a collection of molecules,ions, electrons, chemical substances, etc. Each component in the mixturecan be independently varied. A mixture can consist of two or moresubstances intermingled with no constant percentage composition, whereineach component may or may not retain its essential original properties,and where molecular phase mixing may or may not occur. In mixtures, thecomponents making up the mixture may or may not remain distinguishablefrom each other by virtue of their chemical structure.

These and other aspects of the invention are to be considered exemplaryand non-limiting, and are discussed in greater detail below. The severalaspects of the characterization instruments and methods disclosed andclaimed herein can be advantageously employed separately, or incombination to efficiently characterize a variety of materials, withparticular emphasis on solid materials and polymeric materials. Inpreferred embodiments, these features are employed in combination toform a materials characterization system that can operate as ahigh-throughput screen in a combinatorial materials science researchprogram directed to identifying and optimizing new materials. Suchmaterials appropriate for combinatorial research may include, forinstance, polymers, catalysts, products of various polymerizationreaction conditions, lubricants, gels, adhesives, coatings and/orproducts of new post-synthesis processing conditions. Other materialsappropriate for combinatorial research according to the presentinvention may include, but are not limited to, foodstuffs, cosmetics,beverages, lotions, creams, pharmaceuticals, inks, body fluids, fuels,additives, detergents, surfactants, shampoos, conditioners, dyes, waxes,electrolytes, fuel cell electrolytes, photoresist, semiconductormaterial, wire coatings, hair styling products and the like.

Combinatorial Approaches for Science Research

In a combinatorial approach for identifying or optimizing materials orreactions, a large compositional space (e.g., in the context ofpolymers; of monomers, comonomers, catalysts, catalyst precursors,solvents, initiators, additives, or of relative ratios of two or more ofthe aforementioned) or a large reaction condition space (e.g., oftemperature, pressure and reaction time) may be rapidly explored bypreparing libraries and then rapidly screening such libraries. By way ofillustration, polymer libraries can comprise, for example,polymerization product mixtures resulting from polymerization reactionsthat are varied with respect to such factors.

For example, in the context of polymers (but also applicable to othermaterials), combinatorial approaches for screening a polymer library caninclude an initial, primary screening, in which polymerization productsare rapidly evaluated to provide valuable preliminary data and,optimally, to identify several “hits”—particular candidate materialshaving characteristics that meet or exceed certain predetermined metrics(e.g., performance characteristics, desirable properties, unexpectedand/or unusual properties, etc.). Such metrics may be defined, forexample, by the characteristics of a known or standard polymer orpolymerization scheme. Because local performance maxima may exist incompositional spaces between those evaluated in the primary screening ofthe first libraries or alternatively, in process-condition spacesdifferent from those considered in the first screening, it may beadvantageous to screen more focused polymer libraries (e.g., librariesfocused on a smaller range of compositional gradients, or librariescomprising compounds having incrementally smaller structural variationsrelative to those of the identified hits) and additionally oralternatively, subject the initial hits to variations in processconditions. Hence, a primary screen can be used reiteratively to explorelocalized and/or optimized compositional space in greater detail. Thepreparation and evaluation of more focused polymer libraries cancontinue as long as the high-throughput primary screen can meaningfullydistinguish between neighboring library compositions or compounds.

Once one or more hits have been satisfactorily identified based on theprimary screening, polymer and polymerization product libraries focusedaround the primary-screen hits can be evaluated with a secondaryscreen—a screen designed to provide (and typically verified, based onknown materials, to provide) chemical composition or process conditionsthat relate with a greater degree of confidence tocommercially-important processes and conditions than those applied inthe primary screen. In many situations, such improved“real-world-modeling” considerations are incorporated into the secondaryscreen at the expense of methodology speed (e.g., as measured by samplethroughput) compared to a corresponding primary screen. Particularpolymer materials, catalysts, reactants, polymerization conditions orpost-synthesis processing conditions having characteristics that surpassthe predetermined metrics for the secondary screen may then beconsidered to be “leads.” If desired, additional polymer orpolymerization product libraries focused about such lead materials canbe screened with additional secondary screens or with tertiary screens.Identified lead polymers, monomers, catalysts, catalyst precursors,initiators, additives or reaction conditions may be subsequentlydeveloped for commercial applications through traditional bench-scaleand/or pilot scale experiments.

While the concept of primary screens and secondary screens as outlinedabove provides a valuable combinatorial research model for investigatingpolymers and polymerization reactions, a secondary screen may not benecessary for certain chemical processes where primary screens providean adequate level of confidence as to scalability and/or where marketconditions warrant a direct development approach. Similarly, whereoptimization of materials having known properties of interest isdesired, it may be appropriate to start with a secondary screen. Ingeneral, the systems, devices and methods of the present invention maybe applied as either a primary, secondary or other screen, depending onthe specific research program and goals thereof. See, generally, U.S.patent application Ser. No. 09/227,558 entitled “Apparatus and Method ofResearch for Creating and Testing Novel Catalysts, Reactions andPolymers”, filed Jan. 8, 1999 by Turner, et al., for further discussionof a combinatorial approach to polymer science research. Bulk quantitiesof a particular material may be made after a primary screen, a secondaryscreen, or both.

According to the present invention, methods, systems and devices aredisclosed that improve the efficiency and/or effectiveness of the stepsnecessary to characterize mechanical or physical properties of amaterial sample or a plurality of samples. In preferred embodiments, inthe context of polymer analysis, a property of a plurality of polymersamples or of components thereof can be detected in a polymercharacterization system with an average sample—throughput sufficient foran effective combinatorial polymer science research program.

Referring to FIG. 1, the systems and methods, preferably, start with alibrary or array of sample materials that may exhibit one or morepredetermined physical/mechanical properties. Ultimately, thesepredetermined properties will be determined in a determination step(Step E), however, several prior steps may be effected prior to Step E.The sample materials may be prepared such as by heating, cooling, oraddition of additives. Such preparation is typically designed to affectthe properties that are ultimately being determined. The samplematerials may also be positioned in a desirable manner for propertydetermination. The materials may be positioned on a substrate, a machineor otherwise positioned to assist in ultimately determining propertiesof the materials.

It will be appreciated that one of the advantageous features of thepresent invention is that it affords the ability to screen newly createdmaterials some or all of which are uncharacterized or whose propertiesare unknown prior to the time of screening. Thus, previouslyunidentified and uncharacterized new materials can be screened for acommon selected property. However, this does not prevent the employmentof known references controls or standard as among the library members.

It shall be recognized that sample preparation (Step A) and samplepositioning (Step B) may be optional steps in property determinationprotocols. Also sample preparation and sample positioning may beperformed in any order if they are performed. Additionally it should berecognized that sequences other than the order of steps listed above arepossible, and the above listing is not intended as limiting.

Typically, however, stimulation of the sample materials (Step C) isneeded to effect one or more responses of the materials wherein theresponses are related to the one or more physical properties that arebeing tested. Exemplary stimuli include force, contact, motion and thelike. Exemplary responses include flow, or resistance to flow,deflection, adhesion, deformation, rupture or the like. Negative forces(e.g., compression as opposed to tension, negative pressure as opposedto positive pressure) or the like may be employed.

The responses of the materials are typically monitored (Step D) withhardware such as sensors, transducers, load cells or other like devices.Properties may be determined (Step E) quantitatively or qualitatively byrelating the responses to the material properties.

A plurality of samples may be characterized as described above inconnection with FIG. 1. As a general approach for improving the samplethroughput for a plurality of samples, each of the steps (A) through (E)of FIG. 1 applicable to a given characterization protocol can beoptimized with respect to time and quality of information, bothindividually and in combination with each other. Additionally oralternatively, each or some of such steps can be effected in arapid-serial, parallel, serial-parallel or hybrid parallel-serialmanner.

The throughput of a plurality of samples through a single step in acharacterization process is improved by optimizing the speed of thatstep, while maintaining—to the extent necessary—the information-qualityaspects of that step. Although conventional research norms, developed inthe context in which research was rate-limited primarily by thesynthesis of samples, may find such an approach less than whollysatisfactory, the degree of rigor can be entirely satisfactory for aprimary or a secondary screen of a combinatorial library of samples. Forcombinatorial research (and as well, for many on-line process controlsystems), the quality of information should be sufficiently rigorous toprovide for scientifically acceptable distinctions between the compoundsor process conditions being investigated, and for a secondary screen, toprovide for scientifically acceptable correlation (e.g., values or, forsome cases, trends) with more rigorous, albeit more laborious andtime-consuming traditional characterization approaches.

The throughput of a plurality of samples through a series of steps,where such steps are repeated for the plurality of samples, can also beoptimized. In one approach, one or more steps of the cycle can becompressed relative to traditional approaches or can have leading orlagging aspects truncated to allow other steps of the same cycle tooccur sooner compared to the cycle with traditional approaches. Inanother approach, the earlier steps of a second cycle can be performedconcurrently with the later steps of a first cycle. For example, in arapid-serial approach for characterizing a sample, sample preparation,delivery to a substrate or the like, for a second sample in a series canbe effected before or while the first sample in the series is beingscreened. As another example, a screen of a second sample in a seriescan be initiated while the first sample in the series is being screened.

A characterization protocol for a plurality of samples can involve asingle-step process (e.g., direct measurement of a property of a sampleor of a component thereof) or several steps. In a rapid-serial screenapproach for a single-step process, the plurality of samples and asingle measuring instrument or other instruments are serially positionedin relation to each other for serial analysis of the samples. In aparallel analysis approach, (e.g., as might be employed by itself, or inan upstream or downstream analysis of the samples relative to arapid-serial analysis of the present invention) two or more measuringinstruments or other apparatus are employed to measure properties of twoor more samples simultaneously.

In a serial-parallel approach, a property of a larger number of samples(e.g., four or more) is screened as follows. First, a property of asubset of the four or more samples (e.g., 2 samples) is screened inparallel for the subset of samples, and then serially thereafter, aproperty of another subset of four or more samples is screened inparallel. It will be recognized, of course, that plural measuringinstruments can be employed simultaneous, or plural measuringinstruments can be employed serially.

For characterization protocols involving more than one step,optimization approaches to effect high-throughput characterization canvary. As one example, a plurality of samples can be characterized with asingle characterization system (I) in a rapid-serial approach in whicheach of the plurality of samples (s₁, s₂, s₃ . . . s_(n)) are processedserially through the characterization system (I) with each of the stepseffected in series on each of the of samples to produce a serial streamof corresponding characterizing property information (p₁, p₂, p₃ . . .p_(n)). This approach benefits from minimal capital investment, and mayprovide sufficient throughput—particularly when the steps have beenoptimized with respect to speed and quality of information.

As another example, a plurality of samples can be characterized with twoor more instruments in a pure parallel (or for larger libraries,serial-parallel) approach in which the plurality of samples (s₁, s₂, s₃. . . s_(n)) or a subset thereof are processed through the two or moremeasurement systems (I, II, III . . . N) in parallel, with eachindividual system effecting each step on one of the samples to producethe property information (p₁, p₂, p₃ . . . p_(n)) in parallel. Thisapproach is advantageous with respect to overall throughput, but may beconstrained by the required capital investment.

In a hybrid approach, certain of the steps of the characterizationprocess can be effected in parallel, while certain other steps can beeffected in series. Preferably, for example, it may be desirable toeffect the longer, throughput-limiting steps in parallel for theplurality of samples, while effecting the faster, less limiting steps inseries. Such a parallel-series hybrid approach can be exemplified byparallel sample preparation of a plurality of samples (s₁, s₂, s₃ . . .s_(n)), followed by measuring with a single apparatus to produce aserial stream of corresponding characterizing property information (p₁,p₂, p₃ . . . p_(n)). In another exemplary parallel-series hybridapproach, a plurality of samples (s₁, s₂, s₃ . . . s_(n)) are prepared,measured and correlated in a slightly offset (staggered) parallel mannerto produce the characterizing property information (p₁, p₂, p₃ . . .p_(n)) in the same staggered-parallel manner.

Optimization of individual characterization steps with respect to speedand quality of information can improve sample throughput regardless ofwhether the overall characterization scheme involves a rapid-serial orparallel aspect (i.e., true parallel, serial-parallel or hybridparallel-series approaches). As such, the optimization techniquesdisclosed hereinafter, while discussed primarily in the context of arapid-serial approach, are not limited to such an approach, and willhave application to schemes involving parallel characterizationprotocols that may be employed.

Sample Materials

The samples for which the present invention is useful for screeninginclude polymeric materials or any other liquid, semi-solid, or solidmaterial that is capable of being provided as a high viscosity fluid,solid, or other suitable form. Accordingly, without limitation, purematerials, mixtures of materials, bulk materials, particles ofmaterials, thin films of materials, dispersions of materials, emulsionsof materials, and solutions of materials are all contemplated as withinthe useful scope of the present invention.

In a particularly preferred embodiment, the present invention isemployed for screening polymer samples, or plastic samples includingpolymers. Accordingly, unless otherwise stated, reference to screeningof polymers or other processing of polymers includes plasticsincorporating such polymers. The polymer sample can be a homogeneouspolymer sample or a heterogeneous polymer sample, and in either case,comprises one or more polymer components. As used herein, the term“polymer component” refers to a sample component that includes one ormore polymer molecules. The polymer molecules in a particular polymercomponent can have the same repeat unit, and can be structurallyidentical to each other or structurally different from each other. Forexample, a polymer component may comprise a number of differentmolecules, with each molecule having the same repeat unit, but with anumber of molecules having different molecular weights from each other(e.g., due to a different degree of polymerization). As another example,a heterogeneous mixture of copolymer molecules may, in some cases, beincluded within a single polymer component (e.g., a copolymer with aregularly-occurring repeat unit), or may, in other cases, define two ormore different polymer components (e.g., a copolymer withirregularly-occurring or randomly-occurring repeat units). Hence,different polymer components include polymer molecules having differentrepeat units. It is possible that a particular polymer sample (e.g., amember of a library) will not contain a particular polymer molecule orpolymer component of interest.

In one embodiment, the polymer molecule of the polymer component ispreferably, but need not be, a non-biological polymer. A non-biologicalpolymer is, for purposes herein, a polymer other than an amino-acidpolymer (e.g., protein) or a nucleic acid polymer (e.g.,deoxyribonucleic acid (DNA)). However, the employment of the presentinvention for screening of materials for use as biological implants orprosthetics is contemplated. For instance, the ability of a biologicalpolymer to bind to an agent may be determined from the mechanicalproperty response of a sample of the material in the presence of suchagent. The polymer molecule of the polymer component is, however, notgenerally critical; that is, the systems and methods disclosed hereinwill have broad application with respect to the type (e.g.,architecture, composition, synthesis method or mechanism) and/or nature(e.g., physical state, form, attributes) of the polymer. Hence, thepolymer molecule can be, with respect to homopolymer or copolymerarchitecture, a linear polymer, a branched polymer (e.g., short-chainbranched, long-chained branched, hyper-branched), a cross-linkedpolymer, a cyclic polymer or a dendritic polymer. A copolymer moleculecan be a random copolymer molecule, a block copolymer molecule (e.g.,di-block, tri-block, multi-block, taper-block), a graft copolymermolecule or a comb copolymer molecule.

The particular composition of the polymer molecule is not critical. Thematerial may be thermoplastic, thermoset or a mixture thereof. It may bea polycondensate, polyadduct, a modified natural polymer. Exemplarymaterials include polymers incorporating olefins, styrenes, acrylates,methacrylates, polyimides, polyamides, epoxies, silicones, phenolics,rubbers, halogenated polymers, polycarbonates, polyketones, urethanes,polyesters, silanes, sulfones, allyls, polyphenylene oxides,terphthalates, or mixtures thereof. Other specific illustrative examplescan include repeat units or random occurrences of one or more of thefollowing, without limitation: polyethylene, polypropylene, polystyrene,polyolefin, polyamide, polyimide, polyisobutylene, polyacrylonitrile,poly(vinyl chloride), poly(methyl methacrylate), poly(vinyl acetate),poly(vinylidene chloride), polytetrafluoroethylene, polyisoprene,polyacrylamide, polyacrylic acid, polyacrylate, poly(ethylene oxide),poly(ethyleneimine), polyamide, polyester, polyurethane, polysiloxane,polyether, polyphosphazine, polymethacrylate, and polyacetals.Polysaccharides are also preferably included within the scope ofpolymers. Exemplary naturally-occurring polysaccharides includecellulose, dextran, gums (e.g., guar gum, locust bean gum, tamarindxyloglucan, pullulan), and other naturally-occurring biomass. Exemplarysemi-synthetic polysaccharides having industrial applications includecellulose diacetate, cellulose triacetate, acylated cellulose,carboxymethyl cellulose and hydroxypropyl cellulose. In any case, suchnaturally-occurring and semi-synthetic polysaccharides can be modifiedby reactions such as hydrolysis, esterification, alkylation, or by otherreactions.

In typical applications, a polymer sample is a heterogeneous samplecomprising one or more polymer components, one or more monomercomponents and/or and an additional phase which may be a continuousfluid phase. In copolymer applications, the polymer sample can compriseone or more copolymers, a first comonomer, a second comonomer,additional comonomers, and/or a continuous fluid phase. The polymersamples can, in any case, also include other components, such ascatalysts, catalyst precursors (e.g., ligands, metal-precursors),solvents, initiators, additives, products of undesired side-reactions(e.g., polymer gel, or undesired homopolymer or copolymers) and/orimpurities. Typical additives include, for example, surfactants,fillers, reinforcements, flame retardants, colorants, environmentalprotectants, other performance modifiers, control agents, plasticizers,cosolvents and/or accelerators, among others. In this regard, thepresent invention is particularly attractive for the screening ofeffects of variations of additives upon the characteristics of thematerial. The various components of the heterogeneous polymer sample canbe uniformly or non-uniformly dispersed in the continuous fluid phase.

In one preferred embodiment, the polymer samples of the presentinvention are melted or otherwise heated to a high viscosity fluidstate, with the resulting material constituting a high viscosity fluidsample. Heating may be performed simultaneously while the samples are ona common substrate. Alternatively, the sample is heated to liquefy it ormaintain its liquidity while being transferred to a common substrate(e.g., while in a probe of an automated sampler).

In another embodiment at a point prior to, during, or after depositingthe sample onto the substrate, the polymer sample is preferably,chemically treated to form a liquid polymer sample, such as a polymersolution, a polymer emulsion, a polymer dispersion or a polymer that isliquid in the pure state (i.e., a neat polymer). A polymer solutioncomprises one or more polymer components dissolved in a solvent. Thepolymer solution can be of a form that includes well-dissolved chainsand/or dissolved aggregated micelles. The solvent can vary, depending onthe application, for example with respect to polarity, volatility,stability, and/or inertness or reactivity. Typical solvents include, forexample, tetrahydrofuran (THF), toluene, hexane, ethers,trichlorobenzene, dichlorobenzene, dimethylformamide, water, aqueousbuffers, alcohols, etc. According to traditional chemistry conventions,a polymer emulsion can be considered to comprise one or moreliquid-phase polymer components emulsified (uniformly or non-uniformly)in a liquid continuous phase, and a polymer dispersion can be consideredto comprise solid particles of one or more polymer components dispersed(uniformly or non-uniformly) in a liquid continuous phase. The polymeremulsion and the polymer dispersion can also be considered, however, tohave the more typically employed meanings specific to the art of polymerscience—of being an emulsion-polymerization product anddispersion-polymerization product, respectively. In such cases, forexample, the emulsion polymer sample can more generally include one ormore polymer components that are insoluble, but uniformly dispersed, ina continuous phase, with typical emulsions including polymer componentparticles ranging in diameter from about 1 nm to about 500 nm, moretypically from about 5 nm to about 300 nm, and even more typically fromabout 40 nm to about 200 nm. The dispersion polymer sample can, in suchcases, generally include polymer component particles that are dispersed(uniformly or nonuniformly) in a continuous phase, with typicalparticles having a diameter ranging from about 0.2 um to about 1000 um,more typically from about 0.4 um to about 500 um, and even moretypically from about 0.5 um to about 200 um. Exemplary polymers that canbe in the form of neat polymer samples include dendrimers, and siloxane,among others. The high viscosity fluid polymer sample can also beemployed in the form of a slurry, a latex, a microgel, a physical gel,or in any other form sufficient for creating an array for screeninganalysis as described and claimed herein. In some cases, polymersynthesis reactions (i.e., polymerizations) directly produce highviscosity fluid samples. In other cases, the polymer may be synthesized,stored or otherwise available for characterization in a non-liquidphysical state, such as a solid state (e.g., crystalline,semicrystalline or amorphous), a glassy state or rubbery state. Thepolymer sample can, regardless of its particular form, have variousattributes, including variations with respect to polarity, solubilityand/or miscibility.

In preferred applications, the polymer sample is a polymerizationproduct mixture. As used herein, the term “polymerization productmixture” refers to a mixture of sample components obtained as a productfrom a polymerization reaction. An exemplary polymerization productmixture can be a sample from a combinatorial library prepared bypolymerization reactions, or can be a polymer sample drawn off of anindustrial process line. In general, the polymer sample may be obtainedafter the synthesis reaction is stopped or completed or during thecourse of the polymerization reaction. Alternatively, samples of eachpolymerization reaction can be taken and placed into an intermediatevessels at various times during the course of the synthesis, optionallywith addition of more solvent or other reagents to arrest the synthesisreaction or prepare the samples for analysis. These intermediate samplescan then be characterized at any time without interrupting the synthesisreaction.

It is also possible to use polymer samples or libraries of polymersamples that were prepared previously and stored. Typically, polymerlibraries can be stored with agents to ensure polymer integrity. Suchstorage agents include, for example, antioxidants or other agentseffective for preventing cross-linking of polymer molecules duringstorage. Depending upon the polymerization reaction, other processingsteps may also be desired, all of which are preferably automated.

The polymerization scheme and/or mechanism by which the polymermolecules of the polymer component of the sample are prepared is notcritical, and can include, for example, reactions considered to beaddition polymerization, condensation polymerization, step-growthpolymerization, and/or chain-growth polymerization reactions. Viewedfrom another aspect, the polymerization reaction can be an emulsionpolymerization or a dispersion polymerization reaction. Viewed morespecifically with respect to the mechanism, the polymerization reactioncan be free radical polymerization, ionic polymerization (e.g., cationicpolymerization, anionic polymerization), and/or ring-openingpolymerization reactions, among others. Non-limiting examples of theforegoing include, Ziegler-Natta or Kaminsky-Sinn reactions and variouscopolymerization reactions. Polymerization product mixtures can also beprepared by modification of a polymeric starting materials, by graftingreactions, chain extension, chain scission, functional groupinterconversion, or other reactions.

It will be appreciated that in certain embodiments, a polymer sample isformed in situ on a substrate, post synthesis treated in situ on asubstrate, or a combination thereof. Examples of such post synthesistreatment steps include for instance, heat treating, environmentalexposure (e.g., temperature moisture, radiation, chemicals, etc.), aged,or the like.

In other preferred embodiments, polymer or other sample materials may beprovided as solids or semi-solids. Such samples may be provided in avariety of geometric configurations such as blocks, cylinders, loops,films and the like. Generally, geometric configurations are selected tobe appropriate for one or more tests that are to be performed upon thesamples. Solid and semi-solid samples may be rigid, elastic, gelatinousor otherwise. In one preferred embodiment, samples are provided in atacky state, and thus exhibits at least some degree of adhesivenesswithin the range of temperature under examination. Samples may also bespecifically arranged for testing. For example, samples may beinterwoven as a fabric, unwoven, machined to shape, molded to shape, cutto shape or otherwise physically manipulated for testing.

Sample Size

The sample size is not narrowly critical, and can generally vary,depending on the particular characterization protocols and systems usedto analyze the sample or components thereof. However, it will beappreciated that the present invention advantageously permits forattaining reliable data with relatively small samples. Typical samplesizes can range from about 0.1 microgram to about 1 gram, more typicallyfrom about 1 microgram to about 100 milligrams, even more typically fromabout 5 micrograms to about 1000 micrograms, and still more typicallyfrom about 20 micrograms to about 50 micrograms.

If and when placed on a substrate for forming a library, as discussedherein with regard to sampling, the samples may be dispensed with anysuitable dispensing apparatus (e.g., an automated micropipette orcapillary dispenser, optionally with a heated tip). Each sample of thelibrary is dispensed to an individually addressable region on thesubstrate. Generally, each sample occupies no more than about 1000 mm²of area on a substrate surface, preferably no more than about 100 mm²,more preferably no more than about 50 mm², even more preferably no morethan about 10 mm², most preferably no more than about 5 mm², and it ispossible for a sample to occupy less than about 1 mm². The sample ispreferably to have a thickness that is less than about 500 microns,preferably less than about 100 microns, even more preferably less thanabout 10 microns, most preferably less than about 5 microns, and it ispossible for a sample to have a thickness that is less than about 1microns.

In applications where the sample is disposed in a well, preferably thesample size does not exceed about 1000 milligrams. Accordingly, fordispensing high viscosity fluid samples, the individual samples are eachdispensed in amounts no greater than about 100 ml, more preferably nogreater than about 10 ml and still more preferably no greater than about1 ml.

Libraries of Sample Materials

Libraries of samples have 2 or more samples that are physically ortemporally separated from each other—for example, by residing indifferent regions of a common substrate, in different substrates, indifferent sample containers of a common substrate, by having a membraneor other partitioning material positioned between samples, or otherwise.The plurality of samples preferably has at least 4 samples and more atleast 8 samples. Four samples can be employed, for example, inconnection with experiments having one control sample and three polymersamples varying (e.g., with respect to composition or process conditionsas discussed above) to be representative of a high, a medium and alow-value of the varied factor—and thereby, to provide some indicationas to trends. Four samples are also a minimum number of samples toeffect a serial-parallel characterization approach, as described above(e.g., with two analytical instruments operating in parallel). Eightsamples can provide for additional variations in the explored factorspace. Moreover, eight samples corresponds to the number of parallelpolymerization reactors in the PPR-8™, being selectively offered as oneof the Discovery Tools™ of Symyx Technologies, Inc. (Santa Clara,Calif.), which can be used to prepare polymers for screening inaccordance with the present invention. Higher numbers of samples can beinvestigated, according to the methods of the invention, to provideadditional insights into larger compositional and/or process space. Insome cases, for example, the plurality of samples can be 15 or moresamples, preferably 20 or more samples, more preferably 40 or moresamples and even more preferably 80 or more samples. Such numbers can beloosely associated with standard configurations of other parallelreactor configurations for synthesizing materials for screening herein(e.g., the PPR-48™, Symyx Technologies, Inc.) or of standard samplecontainers (e.g., 96-well microtiter plate-type formats). Moreover, evenlarger numbers of samples can be characterized according to the methodsof the present invention for larger scale research endeavors. Hence, forscreening of polymers or other materials the number of samples can be150 or more, 400 or more, 500 or more, 750 or more, 1,000 or more, 1,500or more, 2,000 or more, 5,000 or more and 10,000 or more samples. Assuch, the number of samples can range from about 2 samples to about10,000 samples or more, and preferably from about 8 samples to about10,000 or more samples. In many applications, however, the number ofsamples can range from about 80 samples to about 1500 samples.

In some cases, in which processing of samples using typical 96-wellmicrotiter-plate formatting or scaling is convenient or otherwisedesirable, the number of samples can be 96*N, where N is an integerranging from about 1 to about 100 or greater. For many applications, Ncan suitably range from 1 to about 20, and in some cases, from 1 toabout 5.

A library of samples comprises two or more different samples spatiallyseparated—preferably, but not necessarily on a common substrate, ortemporally separated. Candidate samples (i.e., members) within a librarymay differ in a definable and typically predefined way, including withregard to chemical structure, processing (e.g., synthesis) history,mixtures of interacting components, post-synthesis treatment, purity,etc. The samples are spatially separated, preferably at an exposedsurface of the substrate, such that the library of samples is separatelyaddressable for characterization thereof. The two or more differentsamples can reside in sample containers formed as wells in a surface ofthe substrate. The number of samples included within the library cangenerally be the same as the number of samples included within theplurality of samples, as discussed above. In general, however, not allof the samples within a library of samples need to be different samples.When process conditions are to be evaluated, the libraries may containonly one type of sample. The use of reference standards, controls orcalibration standards may also be performed, though it is not necessary.Further, a library may be defined to include sub-groups of members ofdifferent libraries, or it may include combinations of plural libraries.The samples of a library may be previously characterized,uncharacterized or a combination thereof, so that property informationabout the samples may not be known before screening.

Typically, for combinatorial science research applications, at least twoor more, preferably at least four or more, even more preferably eight ormore and, in many cases, most preferably each of the plurality ofpolymer samples in a given library of samples will be different fromeach other. Specifically, a different sample can be included within atleast about 50%, preferably at least 75%, preferably at least 80%, evenmore preferably at least 90%, still more preferably at least 95%, yetmore preferably at least 98% and most preferably at least 99% of thesamples included in the sample library. In some cases, all of thesamples in a library of samples will be different from each other.

In one embodiment, preferably at least eight samples are provided in alibrary on a substrate and at least about 50% of the samples included inthe library are different from each other. More preferably, the libraryincludes at least 16 samples and at least 75% of said samples includedin said library are different from each other. Still more preferably,the library includes at least 48 samples and at least 90% of saidsamples included in the library are different from each other.

The substrate can be a structure having a rigid or semi-rigid surface onwhich or into which the library of samples can be formed, mounted,deposited or otherwise positioned. The substrate can be of any suitablematerial, and preferably includes materials that are inert with respectto the samples of interest, or otherwise will not materially affect themechanical or physical characteristics of one sample in an arrayrelative to another. Exemplary polymeric materials that can be suitableas a substrate material in particular applications include polyimidessuch as Kapton™., polypropylene, polytetrafluoroethylene (PTFE) and/orpolyether etherketone (PEEK), among others. The substrate material isalso preferably selected for suitability in connection with knownfabrication techniques. Metal or ceramic (e.g., stainless steel,silicon, including polycrystalline silicon, single-crystal silicon,sputtered silicon, and silica (SiO₂) in any of its forms (quartz, glass,etc.)) are also preferred substrate materials. Other known materials(e.g., silicon nitride, silicon carbide, metal oxides (e.g., alumina),mixed metal oxides, metal halides (e.g., magnesium chloride), minerals,zeolites, and ceramics) may also be suitable for a substrate material insome applications. Another suitable substrate is a silicon wafter thathas been patterned to define a predetermined configuration on which thesample or samples are deposited (e.g., suspended deflectable arms). Asto form, the sample containers formed in, at or on a substrate can bepreferably, but are not necessarily, arranged in a substantially flat,substantially planar surface of the substrate. The sample containers canbe formed in a surface of the substrate as dimples, spots, wells, raisedregions, trenches, or the like. Non-conventional substrate-based samplecontainers, such as relatively flat surfaces having surface-modifiedregions (e.g., selectively wettable regions) can also be employed. Theoverall size and/or shape of the substrate is not limiting to theinvention. The size and shape can be chosen, however, to be compatiblewith commercial availability, existing fabrication techniques, and/orwith known or later-developed automation techniques, including automatedsampling and automated substrate-handling devices. The substrate is alsopreferably sized to be portable by humans. The substrate can bethermally insulated, particularly for high-temperature and/orlow-temperature applications.

In certain preferred embodiments, the substrate is formed to securelymaintain contact with a plurality of samples. According to variousmethodologies it may be desirable to place forces on samples while thesamples remain secured to the substrate. Forces may be applied to thesamples by one or more members separate from the substrate or thesubstrate may apply the forces.

In one particularly preferred embodiment, the library includes acombinatorial library of polymerization product mixtures. Polymerlibraries can comprise, for example, polymerization product mixturesresulting from polymerization reactions that are varied with respect to,for example, reactant materials (e.g., monomers, comonomers), catalysts,catalyst precursors, initiators, additives, the relative amounts of suchcomponents, reaction conditions (e.g., temperature, pressure, reactiontime), post-synthesis treatment, or any other factor affectingpolymerization or material properties. Design variables forpolymerization reactions are well known in the art. See generally,Odian, Principles of Polymerization, 3rd Ed., John Wiley & Sons, Inc.(1991). A library of polymer samples may be prepared in parallelpolymerization reactors or in a serial fashion. Exemplary methods andapparatus for preparing polymer libraries—based on combinatorial polymersynthesis approaches—are disclosed in copending U.S. patent applicationSer. No. 09/211,982 of Turner, et al., filed on Dec. 14, 1998, copendingU.S. patent application Ser. No. 09/227,558 of Turner, et al., filed onJan. 8, 1999, copending U.S. patent application Ser. No. 09/235,368 ofWeinberg, et al., filed on Jan. 21, 1999, and copending U.S. ProvisionalPatent Application Serial No. 60/122,704 entitled “Controlled, StableFree Radical Emulsion and Water-Based Polymerizations”, filed on Mar. 9,1999 by Klaerner, et al. See also, PCT Patent Application WO 96/11878.

Non-Polymer Sample Materials

Although several of the primary applications of the present inventionare directed to combinatorial polymer science research and/or qualitycontrol for industrial polymer synthesis or processing protocols, someaspects of the invention can have applications involving non-polymersamples. A non-polymer sample can be a material that comprises anorganic or an inorganic non-polymer element or compound. For purposesherein, oligomers are considered to be polymers rather thannon-polymers. The non-polymer molecule is, in some cases, preferably anon-biological non-polymer element or compound. Such non-biologicalnon-polymer elements or compounds include non-polymer elements orcompounds other than those having a well-characterized biologicalactivity and/or a primary commercial application for a biological field(e.g., steroids, hormones, etc.). More particularly, suchnon-biological, non-polymer elements or compounds can include organic orinorganic pigments, carbon powders (e.g., carbon black), metals, metalcompounds, metal oxides, metal salts, metal colloids, metal ligands,etc., without particular limitation. Other materials, which may becharacterized according to the present invention include, withoutlimitation, ceramic materials, semiconducting and conducting materials,metal and composites. Still other materials for which the presentapplication finds untility are discussed elsewhere herein.

Sample Handling

Handling of sample materials may be accomplished with a plurality ofsteps which include withdrawing a sample from a sample container anddelivering at least a portion of the withdrawn sample to a substrate.Handling may also include additional steps, particularly and preferably,sample preparation steps. In one approach, only one sample is withdrawninto a suitable liquid or solid dispensing device and only one sampleresides in the probe at one time. In other embodiments, multiple samplesmay be drawn. In still other embodiments, multiple dispensers may beused in parallel.

In the general case, handling can be effected manually, in asemi-automatic manner or in an automatic manner. A sample can bewithdrawn from a sample container manually, for example, with a pipetteor with a syringe-type manual probe, and then manually delivered to aloading port or an injection port of a characterization system. In asemi-automatic protocol, some aspect of the protocol is effectedautomatically (e.g., delivery), but some other aspect requires manualintervention (e.g., withdrawal of samples from a process control line).Preferably, however, the sample(s) are withdrawn from a sample containerand delivered to the characterization system in a fully automatedmanner—for example, with an auto-sampler.

In one embodiment, handling may be done using a microprocessorcontrolling an automated system (e.g., a robot arm). Preferably, themicroprocessor is user-programmable to accommodate libraries of sampleshaving varying arrangements of samples (e.g., square arrays with“n-rows” by “n-columns”, rectangular arrays with “n-rows” by“m-columns”, round arrays, triangular arrays with “r-” by “r-” by “r-”equilateral sides, triangular arrays with “r-base” by “s-” by “s-”isosceles sides, etc., where n, m, r, and s are integers).

Overview of Instruments and Methods

The present invention comprises instruments and methods for screeningthe mechanical or physical properties of a combinatorial library ofmaterials by using at least one response sensing device to measure theresponses of individual library members to forces applied by at leastone force application source selected from the group consisting of afluid, a voltage, a piezoelectric and a combination thereof (hereinafterknown as “FAS”). Referring to FIGS. 2A-2B, there is a flow schematicdiagram of an exemplary automated system 10 for parallel determinationof mechanical properties of a library of materials 11 and a flowchart ofthe general steps for the methods of the present invention Generally,the system 10 includes a suitable protocol design and execution software12 that can be programmed with information such as synthesis,composition, location information or other information related to thelibrary 11 positioned with respect to a substrate or substrates. Theprotocol design and execution software 12 is typically in communicationwith instrument control software 14 for controlling the instrument 16having at least one FAS 18 and at least one response sensing device 20.The protocol design and execution software 12 is also in communicationwith data acquisition hardware/software 22 for collecting data fromresponse sensing device 20. Preferably, the instrument control software14 commands the FAS 18 of the instrument 16 to apply force to eachlibrary member 11 in an effort to evoke a response from such librarymember 11. The actual displacement of each library member 11 by suchforce may be small (e.g., about 30 μm or less). At substantially thesame time, the response sensing device 20 of the instrument 16 monitorsthe response of the library member 11, the force being applied to thelibrary member 11 or both and provides data on the response to the dataacquisition hardware/software 22. Thereafter, the instrument controlsoftware 14, the data acquisition hardware/software 22 or both transmitdata to the protocol design and execution software 12 such that eachlibrary member 11 or information about each library member 11 may bematched with its response to the applied force and transmitted as datato a database 24. Once the data is collected in the database, analyticalsoftware 26 may be used to analyze the data, and more specifically, todetermine mechanical properties of each library member 11, or the datamay be analyzed manually.

In a preferred embodiment, the system 10 is driven by suitable softwarefor designing the library, controlling the instruments for mechanicalproperty screening, and data acquisition, viewing and searching, such asLIBRARY STUDIO™, by Symyx Technologies, Inc. (Santa Clara, Calif.);IMPRESSIONIST™, by Symyx Technologies, Inc. (Santa Clara, Calif.);EPOCH™, by Symyx Technologies, Inc. (Santa Clara, Calif.); or acombination thereof. The skilled artisan will appreciate that theabove-listed software can be adapted for use in the present invention,taking into account the disclosures set forth in commonly-owned andcopending U.S. patent application Ser. No. 09/174,856 filed on Oct. 19,1998, U.S. patent application Ser. No. 09/305,830 filed on May 5, 1999and WO 00/67086, U.S. patent application Ser. No. 09/420,334 filed onOct. 18, 1999, U.S. application Ser. No. 09/550,549 filed on Apr. 14,2000, each of which is hereby incorporated by reference. Additionally,the system may also use a database system developed by SymyxTechnologies, Inc. to store and retrieve data with the overlays such asthose disclosed in commonly-owned and copending U.S. patent applicationSer. No. 09/755,623 filed on Jan. 5, 2001, which is hereby incorporatedby reference for all purposes. The software preferably providesgraphical user interfaces to permit users to design libraries ofmaterials by permitting the input of data concerning the preciselocation on a substrate of a material (i.e., the address of thematerial). Upon entry, the software will execute commands to controlmovement of the robot, for controlling activity at such individualaddress. The versatile instruments and methods of the present inventioncan screen libraries of materials based on many different mechanicalproperties relating to Young's modulus (e.g., flexure, uniaxialextension, biaxial compression, and shear), failure (stress and strainat failure, toughness), adhesion, and others.

The instruments and methods of the present invention can conductparallel, rapid-serial, serial-parallel and hybrid parallel-serialmechanical properties characterization. Some instruments and methodsembodiments of the present invention are directed to parallelcharacterization of material samples, while others are directed to rapidserial or serial-parallel characterization of material samples.Throughout this specification, the specific preferred embodimentsdiscussed in detail below are parallel embodiments. These particularlypreferred embodiments have many detailed features, which may not benecessary in other embodiments of this invention. For example, lessnumber of FAS and/or response sensing devices may be required in therapid serial embodiments compared to the preferred parallel embodimentsdiscussed below. Another example is that response sensing devices areplaced remotely to the samples and are set at certain spacing in thepreferred parallel embodiments discussed below. Those of skill in theart can easily modify such design parameters for other embodiments, suchas by placing the response sensing devices at other spacing, not placingthe response sensing devices substantially in a plane, etc. These aredesign choices for the present invention and describe other embodimentsof the invention.

The several aspects of the characterization methods and systemsdisclosed and claimed herein can be advantageously employed separately,or in combination to efficiently characterize a variety of materials,with particular emphasis on polymeric materials. In preferredembodiments, these features are employed in combination to form apolymer characterization system that can operate as a high-throughputscreen in a materials science research program directed to identifyingand optimizing new materials, for instance, new polymers, new catalysts,new polymerization reaction conditions and/or new post-synthesisprocessing conditions. Certain characterizing information—particularlyinformation obtainable from the present invention are broadly useful forcharacterizing polymers and polymerization reactions. As such, theparticular materials and/or mechanisms disclosed herein should beconsidered exemplary of the invention and non-limiting as to the scopeof the invention, which may be applicable in a variety of applications.

Bulge Test Instrument

A bulge test instrument 100 is a preferred instrument of the presentinvention to measure mechanical properties of a library of materials102. Referring to FIGS. 3-5, the instrument 100 is generally comprisedof a mounting member that is adapted for defining a substantiallygas-tight vessel 104, e.g., a block having a plurality of openings 106to which the library of materials 102 is removably secured across theopenings 106 for screening, at least one FAS 110 that is a pressurevarying device 111 in combination with at least one fluid (not shown)that transmits the pressure (i.e., force) supplied by pressure varyingdevice 111 to the library members 102, and at least one response sensingdevice 112 to measuring the response of each library member 102 to theforces delivered by the FAS 110. The vessel 104 can be constructed ofany material, but it is preferably constructed of a sufficiently rigidmaterial that the dimensions of the vessel do not change appreciably inresponse to changes in differential pressure. Examples of a preferredrigid material includes, without limitation, aluminum and stainlesssteel.

The securing of each library member 102 to the vessel 104 can beaccomplished in any number of ways such as mechanically, magnetically,electromagnetically, electromechanically, chemically or a combinationthereof. For example, the library member 102 can be secured across itsrespective opening by a mechanical clamp, an adhesive, or a combinationof both. Referring to FIG. 5, the library of materials 102 is preferablyplaced on discrete and predefined regions 114 of a substrate orsubstrates 116. It is also preferred that the substrate is a flexiblematerial. The predefined regions 114 generally correspond to unsecuredor unclamped portions of the substrate(s) 116, which in FIG. 5, coincidewith the openings 106 in the vessel 104. Useful substrate 116 materialsinclude plastic sheets, such as a polyimide film, which may ranges inthickness on the order of from about 10 μm to about 100 μm. The librarymembers 102 generally have comparable thickness, and preferably areabout 20 μm thick. In some cases, clamping or fastening may beinsufficient to secure the substrate(s) 116 to the vessel 104. Thus, inan alternative embodiment, the substrate(s) 116 may be bonded to thevessel 104 using a pressure sensitive adhesive. The adhesive should beless compliant than the substrate(s) 116, and during its application,care is taken to ensure a uniform bond line adjacent to the openings106.

As discussed above, various methods can be used to make the library 102.For example, a library 102 comprised of polymers can be prepared bydepositing known amounts of high viscosity fluid or solid materials 102at the predefined regions 114 on substrate(s) 116. Following deposition,the library materials 102 and substrate(s) 116 are preferably compressedunder melt-flow conditions to create polymer films of requisitethickness. Alternatively, the library members 102 can be dissolved inone or more solvents and deposited at the predefined regions 114 on thesubstrate(s) 116 using conventional liquid handling techniques such asautomated pipetting. To prevent liquid library members 102 fromspreading beyond their respective predefined regions 114, thesubstrate(s) 116 are pretreated—e.g., by selective etching or by silanetreatment—to modify the surface energy of the substrate(s) 116 in or outof the predefined regions 114. See, for example, co-pending U.S. patentapplication entitled “Formation of Combinatorial Arrays of MaterialsUsing Solution-Based Methodologies,” Ser. No. 09/156,827, filed Sep. 18,1998, and co-pending U.S. patent application, “Polymer Libraries on aSubstrate, Method for Forming Polymer Libraries on a Substrate andCharacterization Methods With Same,” Ser. No. 09/567,598, filed May 10,2000, each is herein incorporated by reference. Upon deposition, theliquid library members 102 are confined to predefined regions 114 havinglike surface energies, and form solid films following evaporation of thesolvent. After brief annealing under vacuum to remove residual solvent,the thickness at the center or other location of each library member 102can be measured using a variety of art disclosed techniques, includingoptical reflection profilometry, optical interference profilometry, orthe like. In another embodiment, metallic, organometallic, or othercompounds can be directly deposited on the substrate(s) 116 by chemicalvapor deposition, physical vapor deposition, or similar art disclosedtechniques.

In some instances, the size and placement of the library members 102 onthe substrate(s) 116 can affect the measurements. Although thin filmsmade by solution deposition techniques often have relatively uniformthickness near their centers, they exhibit substantial variation awayfrom their centers, which can influence flexural measurements. To helpminimize edge effects, library members 102 made by solution depositiontechniques should generally extend beyond the regions defined by theopenings 106.

The FAS 110 operates by having its pressure varying device 111 applypressure to at least one library member 102 through a transmission fluid(i.e., gas or liquid). Examples of a pressure varying device 111include, without limitation, a piston connected to the vessel 104 thatvaries the pressure within the vessel 104 by mechanical compression orexpansion of a transmission fluid; a temperature controller for varyingthe temperature of a transmission fluid; a heat transfer device such asa resistance heater, a liquid-liquid heat exchanger that is connected toa reservoir of exchange fluid, a liquid-gas heat exchanger that isconnected to a reservoir of exchange fluid, and a combination thereof.If a heat transfer device is used as the pressure varying device 111,then the region of transmission fluid that is heated or cooled ispreferably separated from the region surrounding each library member 102so as to minimize changes in the temperature of the library member 102.This is more easily achieved with gaseous transmission fluids, where thechange in pressure within temperature is relatively large and thethermal conductivity of the medium is relatively low compared to liquidtransmission fluids.

Pressure may be varied across more than one library member 102simultaneously. This approach generally reduces the complexity of theinstrument but may lead to a less robust instrument, as the mechanicalfailure of one secured library member 102 are likely to affect all otherlibrary members 102 that share the same FAS 110. Thus, it is preferredthat each library member 102, secured across its respective opening 106within the vessel 104, has its own FAS 110, response sensing device 112or both. For clarity purpose, FIG. 3 only shows one response sensingdevice 112, but the present invention is not limited to having oneresponse sensing device 112. For example, for some parallel embodiments,the instrument 100 may have numerous response sensing devices 112 up to,and even beyond, the number of members in the library 102. It is alsoacceptable to less number of response sensing devices 112 compared tothe number of members in the library 102. Alternatively, the responsesensing device 112 can be configured to translate in an x-y direction tomeasure the response of each library member 102 to the applied force oneat a time in a rapid serial fashion.

The transmission fluid transmits the pressure variation generated by thepressure varying device 111 within the vessel 104 to its respectivelibrary member(s) 102. The transmission fluid is preferably chosen so asto be chemically inert with respect to the internal components of thevessel 104, and/or to the respective library member(s) 102. Thecompressibility of the transmission fluid is preferably chosen so thatthe means of varying the internal pressure is capable of generatingpressure changes of the desired magnitude. Examples of a suitabletransmission fluid include, without limitation, air, argon, hydrogen,nitrogen, helium, fluorocarbon liquids, ethanol, water, mercury, andmixture thereof. Fluorocarbon liquids, ethanol, and water are preferredtransmission fluids for less compliant materials such as thin metalfoils and mercury may be a suitable transmission fluid for extremelystiff material requiring extremely large pressure changes. In the eventof a conflict between these requirements, two or more fluids may be usedto transmit the pressure variation within the vessel 104. In thisalternative preferred embodiment, the vessel 104 is designed such thatone of the fluids remains in contact with its respective librarymember(s) 102 while the other fluid remains in contact with the pressurevarying device 111, and both fluids are mutually immiscible. Theseparation of these fluids is preferred to be maintained throughgravity, surface tension, or a mixture thereof.

The response (i.e., displacement) of each library member 102 to thepressure transmitted by the transmission fluid and applied by thepressure varying device 111 is measured by a response sensing device 112as shown in FIG. 3. The response sensing device 112 can be a variety ofcommercially available electronic pressure sensors. Alternatively, theresponse sensing device 112 can measure the response optically,electrically, or via a dual pressure system.

Optical Response Sensing Devices

The response sensing device 112 can measure the response of each librarymember 102 to the force applied by the FAS 110 optically using artdisclosed methods such as optical reflectance, optical interferometry,shadow illumination, and others. Examples of commercially availableoptical sensing devices 112 are Keyence Displacement Sensors Model Nos.LC-2450 and LC-2430 manufactured by Keyence Corporation (Woodcliff Lake,N.J.).

Optical reflectance generally involves illuminating the surface of eachlibrary member 102 by a highly collimated, monochromatic light sourceplaced at a slight angle to the normal of the plane of the undeflectedlibrary member 102 and a detector aligned so as to detect the lightscattered or reflected from the surface of the library member 102.Change in the height of the library member 102 produce changes in thesignal received by the detector. Examples of a suitable light sourceinclude, without limitation, light emitting diodes (LEDs) and lasers.Examples of a suitable detector include, without limitation, acharge-coupled device (CCD), a photomultiplier, an avalanche photodiode,or an amplified photodiode.

Optical interferometry generally involves illuminating the surface ofeach library member 102 by a laser beam (monochromatic or polychromatic)with an incident beam directed along the normal to the plane of theundeflected library member by an optical train. The library member 102and the end of the optical train define an optical cavity whose lengthis given by the distance from the end of the train to the surface of thelibrary member 102. Some fraction of the incident beam is reflected fromthe surface of the library member 102, and the reflected and incidentbeams interfere. The optical train generally includes an element thatsplits the light reflected back from the surface of the library member102 and directs part of the reflected light to a detector. Examples of asuitable optical train include, without limitation, appropriatelyaligned half-silvered mirrors, fiber optic beamsplitters, and the like.If a polychromatic light source is used, the split signal is then passedthrough or reflected from a diffraction grating (not shown) in order toseparate the light into its spectral components. Examples of a suitabledetector for both monochromatic and polychromatic light sources include,without limitation, a charge-coupled device (CCD), a photomultiplier, anavalanche photodiode, an amplified photodiode, and the like. For amonochromatic light source, variation in the optical train to thelibrary member 102 distance generally produces a periodic variation inthe intensity of the signal received at the detector. For apolychromatic light source, the signal receives by the detector displaysa frequency-dependent oscillation in intensity which depends on theabsolute value of the optical train to the library member distance.

Shadow illumination generally involves illuminating the surface of eachlibrary member 102 by a light source with an incident beam directed atan angle to the normal of the plane of the undeflected library member102. The light reflected from the library member 102 and surroundingsupport is generally detected at a second, large angle with respect tothe normal plane of the library member 102 by a detector. Examples of asuitable light source includes, without limitation, light-emittingdiodes, conventional lamps, and the like. As the library member 102 isdisplaced by the pressure transmitted by the transmission fluid andapplied by the FAS 110, some fraction of the reflected light is blockedby the library member 102, and some fraction of the light is reflectedaway from the detector. In one preferred embodiment, the detectormeasures the intensity of the light signal. Changes in this intensityare related to variation in the shape of the library member 102 as it isbeing deformed or displaced. Examples of a suitable detector for thisembodiment include, without limitation, photodiodes andphototransistors. In another preferred embodiment, the detector is animaging detector (e.g., a CCD) that records the shadow cast by thedisplaced library member and subsequent analysis may be performed toyield the shape of the library member.

Electrical Response Sensing Devices

The response sensing device 112 can measure the response of each librarymember to the force applied by the FAS 110 electrically using artdisclosed methods such as capacitance, resistance, tunneling,electromechanical switching systems, or others.

One preferred capacitance method generally involves placing a commercialcapacitive sensor in close proximity to the surface of each librarymember 102. The changes in the distance between the library member 102and the capacitive sensor alter the combined capacitance of thecapacitive sensor and the surrounding environment, resulting in ameasurable voltage reading. An alternative capacitance method generallyinvolves using a flexible and conductive material as the substrate(s)116 (e.g., a piece of polyester coated with a thin layer of aluminum).The composite that is formed by each library member 102 and itsrespective substrate 116 is positioned in close proximity to a metalplate. The composite and the metal plate form a parallel plate capacitorin which the composite and the metal plate form the two electrodes. Ifthe library member 102 is semiconducting or insulating, it behaves as adielectric between the two plates of this capacitor. If the librarymember 102 is conducting, the electrical contact between the compositeessentially makes the library sample 102 the first plate of thecapacitor. Variation in the pressure across the composite produceschanges in its shape that in turn lead to changes in the capacitance ofthe system. The changes in capacitance are detected by art disclosedtechniques.

One preferred resistance method generally involves having a substrate116 that exhibits changes in electrical resistance as a function ofdisplacement. Examples of a suitable substrate 116 include, withoutlimitation, polyimide, poly(ethylene terephthalate), a piezoresistivematerial, and the like. Measurements of the resistance of each librarymember 102 and its respective substrate 116 are preferably used todetermine the displacement of the library member 102. In an alternativepreferred embodiment, the substrate(s) 116 are diaphragm strain gages.Each diaphragm strain gage include two strain gages generallyconstructed out of two polyimide films enclosing a piezoresistive wirepath made of stainless steel foil. Variations in the pressure across thesubstrate 116 lead to displacement of the substrate with its respectivelibrary member 102, which implies changes in the dimensions andresistance of the piezoresistive material.

The tunneling method generally involves having the substrate 116 with aconductive backing and a conducting electrode in the form of a sharp tipplaced sufficiently close to the substrate 116 and its respectivelibrary member 102 so that when a known voltage is applied, electronscan tunnel from the tip to the substrate 116 or vice versa, depending onthe sign of the voltage, resulting in a measurable current. This currentdepends exponentially on the tip and the substrate 116 separation,making this tunneling system a very sensitive technique for measuringdisplacement.

The electromechancial switching method generally involves having amechanical contact between each displaced library member 102 and an artdisclosed electromechanical assembly to complete or break a circuitpath, thereby signaling that the displacement of the library member 102has reached a particular value. The electromechanical assembly 112 ispreferred engineered so that the forces resulting from this contact arenegligible in comparison to those associated with displacement of thelibrary member.

Dual Pressure Response Sensing Device

The dual pressure method generally involves securing each library member102 between the vessel 104 and a second smaller vessel filled with apressure transmission fluid and connected to a pressure sensor. Thesecuring of each library member 102 between the two vessels can beaccomplished in any number of ways such as mechanically, magnetically,electromagnetically, electromechanically, chemically or a combinationthereof. Examples of suitable pressure transmission fluid and pressuresensor 126 are the same as described above. The displacement of thelibrary member 102 is generally calculated based upon the volumeenclosed by the second smaller vessel and the pressure measured by thepressure sensor.

Screening Using the Bulge Test Instrument

In a preferred method of the present invention for high throughputmechanical property screening, the library of materials 102 areremovably secured across the openings 106 of the vessel 104 so part ofeach library member 102 is suspended over its respective opening 106.Force is then applied by the FAS 110 to the library through the FAScomponents—the pressure varying device 111 applying pressure to thetransmission fluid, which transmits it to the library members 102. Theapplied pressure can vary (e.g., monotonically, sinusoidally,discontinuously or impulse like, etc.). The response (i.e.,displacement) of each library member 102 to the pressure is monitored byits respective response sensing device 112 and used to determine themechanical properties of the library member 102 based upon art disclosedanalytical models. See, e.g., W. C. Young, Roark's Formulas for Stressand Stain, 1989; S. Timoshenko, Theory of Plates and Shells,McGraw-Hill, New York 1940. For example, when the pressure is appliedacross the library member 102 increases or decreases monotonicallycausing displacement of such library member 102, the displacement can beused to measure the flexure rigidity D of the library member 102 asshown here: $w = \frac{P\quad a^{4}}{64D}$

where w is the library member's 102 center displacement, P is theapplied pressure, and a is the library member's 102 radius. With theflexure rigidity value, the library member's Young's modulus E can alsobe measured: $E = \frac{12{D\left( {1 - v^{2}} \right)}}{h^{3}}$

where h is the library member's thickness and v is Poisson's ratio.Poisson's ratio may be the same for all members across the library 102if they are all derived from the same or similar materials. Smallvariation in Poisson's ratio value across the library does not affectthe result significantly as it is generally less than 0.5 and its squareis much less than 1 (e.g., 0.3 for latexes). Once the Young's modulus ofeach library member 102 is known, other mechanical properties of thelibrary member 102 such as uniaxial extension, biaxial compression,shear, glass transition temperature, melting point, toughness, stressand stain at failure, and others may also be derived using art disclosedtechniques and analytical models. The mechanical properties that arepreferably measured using the bulge test instrument 100 in accordancewith the present invention include each library member's complex spectraof flexural rigidity and its complex spectra of Young's modulus withinDC-1000 Hz frequency range and −100° C. to +200° C. temperature range.

Capacitive Pull-In Instrument

A capacitive pull-in instrument 200 is a preferred instrument of thepresent invention to measure mechanical properties of a library ofmaterials 202. Referring to FIG. 6, the capacitive pull-in instrument200 is generally comprised of a plurality of capacitors 204 with eachcapacitor 204 having a first structure 206 and a second structure 208,wherein both structures (206, 208) are conductors of known Young'smodulus and have dimensions that are electrically insulated from oneanother; at least one FAS 210; and at least one response sensing device212. To help make the capacitive pull-in instrument more robust, it ispreferred that each library member 202 has its own FAS 210 and/orresponse sensing device 212.

It is preferred that the first structure 206 and the second structures208 are planar structures. However, structures of other shapes (e.g.,circular, cured, bended, angular, or others) can also be used to formthe two structures (206, 208). The structures (206, 208) preferablyinclude a means of making electrical connections to each other in orderto place a voltage across them. An example of such means of makingelectrical connections is metal contact points (e.g., electrodes) 214placed on the structures (206, 208) by art disclosed techniques (e.g.,vapor deposition). The structures (206, 208) are preferably separatedfrom one another by at least one region 216, which may optionally befilled with a dielectric fluid (not shown). The structures (206, 208),in the absence of an applied voltage, are preferably maintained at afixed distance by a suitable structure, force (e.g., magnetic) or thelike 214. In a preferred embodiment, the structures (206, 208) areplanar and they are maintained at a fixed distance by at least onespacer 218 attached to and positioned between them. The spacer 218 ispreferably located at the edge of the structures (206, 208) so as toform a cantilever or other suspended structure, as shown in FIG. 6.Alternatively, the spacer 218 may be positioned at the center of thestructures (206, 208). Another alternative is extending the spacer 218around the perimeter of the structures (206, 208), which provides anadditional advantage of preventing the individual library members fromflowing or otherwise moving into the regions 216 between the structures(206, 208). Such overflow may prevent the desired occurrence ofcapacitive pull-in. The spacer 218 is preferably constructed of aninsulating material (e.g., polyimide).

At least one FAS 210 varies the voltage applied to the capacitors 204.Examples of suitable FAS 210 include, without limitation, a variablevoltage power supply, a combination of a programmable constant currentsource for charging the capacitor and a voltmeter for measuring thevoltage difference across the capacitor, and the like. At least oneresponse sensing device 212 is required to monitor the responses of thecapacitors 204 and the library members 202 to the applied voltage.Examples of suitable response sensing devices 212 include, withoutlimitation, the response sensing devices described above for the bulgetest instrument 100 relating to optical reflectance, opticalinterferometry, shadow illumination, capacitance (using a high-frequencyvoltage signal superimposed on the DC voltage signal to measure thecapacitance of the instrument 200), resistance (using a strain gageattached to one of the structures (206, 208), and electromechanicalswitching. Another preferred response sensing device 212 is toincorporate it into the structures (206, 208) by constructing one regionon each of the planar structures from a semiconducting material (e.g., awafer sensor). The region of the first structure 206 is p-doped and theregion on the second structure 208 is n-doped or vice versa. Uponcapacitive pull-in, these regions are brought into contact forming adiode across each of the capacitors 204 and resulting in a discontinuousdrop in the voltage across each of the capacitors 204. For claritypurpose, FIG. 6 only shows one response sensing device 212, but thepresent invention is not limited to having one response sensing device212. For example, for some parallel embodiments, the instrument 200 mayhave numerous response sensing devices 212 up to, and even beyond, thenumber of members in the library 202. It is also acceptable to lessnumber of response sensing devices 112 compared to the number of membersin the library 102. Alternatively, the response sensing device 212 canbe configured to translate in an x-y direction to measure the responseof each library member 202 to the applied force one at a time in a rapidserial fashion.

It is preferred that the plurality of capacitors 204 are assembled in amonolithic unit using semiconductor fabrication techniques in which theyare made from a single wafer as shown in FIG. 6. In an alternativepreferred embodiment, the plurality of capacitors 204 are assembled fromphysically separate components such as forming the structures (206, 208)from two separate wafers and the spacers 218 are produced by depositinginsulating materials on selected regions of one or both wafers. Anexample of this alternative is using a disposable, flexible substratesuch as polyimide on which metal has been deposited on one side inselected regions to produce a plurality of the first structures 206 andassociated electrical contact points 210. The other side of thisflexible substrate is coated with an adhesive to facilitate attachmentto the spacers 218. To complete the plurality of capacitors 204, anidentical flexible substrate, with selective deposition of metals orother conducting materials to act as electrical contact points 210,serves as the second planar structures 208 is also attached to thespacers 218. Alternatively, the second planar structures 208 may beconstructed of a rigid material (e.g., silicon wafer) with appropriatelypositioned conducting and insulting regions. After the mechanicalproperty screening, the flexible substrates forming the plurality ofcapacitors 204 may be removed from the instrument 200 and discarded,eliminating the need to clean the instrument 200 between screenings.

Screening Using the Capacitive Pull-In Instrument

In a preferred method of using the capacitive pull-in instrument 200 tomeasure mechanical properties of the library of materials 202, a voltageis applied by at least one FAS 210 across the capacitors 204 causingelectric charges of opposite sign to accumulate on the planar structures(206, 208) resulting in applying one or more forces on each of them(206, 208). The one or more forces cause a displacement of thestructures (208, 210), which increases the capacitance of the capacitors204 resulting in a slight increase in the quantity of accumulatedelectrical charge on the structures (206, 208). The increase in thequantity of accumulated electrical charge on the structures (206, 208)again causes more force to be applied on each of the structures (206,208) resulting in additional displacement. The displacements can beexpressed, for instance, as a geometric series. The voltage applied bythe at least one FAS 210 can be non-oscillatory or oscillatory. For lowvoltages, the series typically converges to a finite value, which isconsiderably less than the separation of the structures (206, 208), andthe instrument 200 is mechanically stable. However, for high voltages,the series may not converge, and the capacitors 204 become mechanicallyunstable causing the structures (206, 208) to draw together. The voltageat which this instability occurs (i.e., the pull-in voltage) depends onthe shape and mechanical properties of the structures (206, 208).Accordingly, using art disclosed analytical models, a measurement of thepull-in voltage can be used to extract the mechanical properties of thestructures (206, 208) in the absence of any library member 202. See,e.g., P. M. Osterberg and S. D. Senturia, “M-TEST: A Test Chip for MEMSMaterial Property Measurement Using Electrostatically Actuated TestStructures,” Journal of Microelectromechanical Systems, Vol. 6, No. 2,June 1997 and is incorporated herein by reference. Thereafter, thelibrary members are individually secured onto the first structures 206as shown in FIG. 6. The securing of each library member 202 to itsrespective first structure 206 can be accomplished in any number of wayssuch as mechanically, magnetically, electromagnetically,electromechanically, chemically or a combination thereof. A voltage isagain applied by at least one FAS 210 across the capacitors 204, theresulting pull-in voltage is measured again, and the ratio between thelibrary 202 present and the library 202 absent values is determined andYoung's modulus of each library member 202 can be calculated using artdisclosed analytic models. Once the Young's modulus of each librarymember 202 is known, other mechanical properties of the library member202 such as flexure, uniaxial extension, biaxial compression, shear,glass transition temperature, melting point, toughness, stress and stainat failure, adhesion, and the like may also be derived using artdisclosed techniques and analytical models. The mechanical propertiesthat are preferably measured using the capacitive pull-in instrument 200in accordance with the present invention include each library member'scomplex spectra of flexural rigidity and its complex spectra of Young'smodulus within DC-1000 Hz frequency range and −100° C. to +200° C.temperature range.

Piezoelectric Instrument

A piezoelectric instrument 300 is a preferred instrument of the presentinvention to measure mechanical properties of a library of materials302. Referring to FIGS. 7-9, the piezoelectric instrument 300 isgenerally comprised of a supporting frame 303 containing a plurality ofpiezoelectric benders 304 (illustrated as disk benders), each having abacking plate 306, an electrode 308, and an appropriately polarizedceramic disk 310; at least one FAS 312 that is preferably a variablevoltage supply source; and at least one response sensing device 314. Thebacking plate 306 is preferably constructed out of a metal, morepreferably, brass or stainless steel. The electrode 308 is preferablysintered, glued, fastened, or otherwise joined to the backing plate 306.

The library members 302 are secured to the backing plates 306. Thesecuring of each library member 302 to its respective backing plate 306can be accomplished in any number of ways such as mechanically,magnetically, electromagnetically, electromechanically, chemically or acombination thereof. It is preferred that the library members 302 aredirectly deposited onto the backing plates 306. Alternatively, a thinlayer of coupling liquid can be used to secure the library members 302to the backing plates 306.

Voltage is applied to each library member 302 via the voltage supplysource 312 to the electrode 308 triggering a change in the diameter ofthe ceramic disk 310 and thereby causing the entire bender 304 to buckleas shown in FIG. 10. Referring to FIG. 8, small part of the electrode308 on the bender 304 can be separate out so that the stress field inthe ceramic disk 310 is not considerably disturbed. This electrode 308and a part of the bender 304 underneath can be used as the responsesensing device 314. Other suitable response sensing devices 314 include,without limitation, the optical response sensing devices described abovefor the bulge test instrument 100 relating to optical reflectance,optical interferometry, and shadow illumination. For clarity purpose,FIG. 7 only shows one response sensing device 314, but the presentinvention is not limited to having one response sensing device 314. Forexample, for some parallel embodiments, the piezoelectric instrument 300may have numerous response sensing devices 314 up to, and even beyond,the number of members in the library 302. Alternatively, the responsesensing device 314 can be configured to translate in an x-y direction tomeasure the response of each library member 302 to the applied force oneat a time in a rapid serial fashion. To make the piezoelectricinstrument 300 more robust, it is preferred that each library member 302has its own voltage supply source 312 and response sensing device 314.

In an alternative preferred embodiment of the piezoelectric instrument300, the benders 304 are replaced a plurality of piezoelectric elementseach having with a sensor region and an actuator region. Alternatively,each piezoelectric element can be replaced by a separate piezoelectricsensor element and a separate piezoelectric actuator element connectedto each other by a platform.

Screening Using the Piezoelectric Instrument

In a preferred method of using the piezoelectric instrument 300 tomeasure mechanical properties of the library of materials, a voltage,preferably sinusoidally, is applied by at least one variable voltagesupply source 312 to the benders 304 causing their ceramic disks 310 togenerate a stress field across each library member 302. The resultingstrain in each library member 302 is measured by its respective responsesensing device 314. Using art disclosed analytic models, the Young'smodulus of each bender 304, without the library present, is obtained.Thereafter, the library members 302 are secured onto the backing plates306 of the benders 304 and another voltage is applied by the at leastone variable voltage supply source 312 at variable frequency to thebenders 304 resulting in the application of sinusoidal pressure to thelibrary 302 and the benders 304. Voltage across the response sensingdevices 314 is proportional to each library member's displacement andcan be used to calculate the Young's modulus of each library member 302based upon art disclosed analytical models. Once the Young's modulus ofeach library member 302 is known, other mechanical properties of thelibrary member 202 such as flexure, uniaxial extension, biaxialcompression, shear, glass transition temperature, melting point,toughness, stress and stain at failure, or others may also be derivedusing art disclosed techniques and analytical models. The mechanicalproperties that are preferably measured using the piezoelectricinstrument 300 in accordance with the present invention include eachlibrary member's complex spectra of flexural rigidity and its complexspectra of Young's modulus within DC-1000 Hz frequency range and −100°C. to +200° C. temperature range.

Environmental Control Device

Since the mechanical properties of materials can depend strongly onenvironmental conditions—temperature, pressure, ambient gas composition(including humidity), electric and magnetic field strength, and soon—the screening instruments discussed above may include a controlsystem for regulating environmental conditions as shown in FIG. 11.Useful control systems include an environmental chamber that enclosesthe sample, the sample holder, and the FAS. The system may also usescomputer software to regulate conditions in the environmental chamber.As discussed below, the system may locate the response sensing deviceoutside of the environmental chamber if their performance is stronglyinfluenced by any of the environmental control variables, such astemperature. Measurements may be performed as a function of the value ofone or more of these quantities, or may be performed as a function oftime elapsed after a change in the value of one or more of thesequantities. The means by which these changes may be produced aredescribed in detailed in the commonly owned U.S. Pat. No. 6,157,449 andU.S. patent application Ser. No. 09,579,338 titled “Rheo-Optical indexerand Method of Screening and Characterizing Arrays of Materials”, filedon May 25, 2000 (Carlson, et al.), which is incorporated herein byreference for all purposes.

Screening Throughput

The instruments described above in accordance with the present inventioncan screen a library having 2 or more material samples, and preferably,at least 8 samples to ensure adequate screening throughput. Those ofskill in the art will appreciate that lower or higher throughput mayserve the needs of a particular application of this invention. Thus, 4or more, 8 or more, 16 or more, 24 or more, or 48 or more FAS and/orresponse sensing devices in parallel are within the scope of thisinvention.

For methods directed to characterizing a plurality of samples, aproperty of each of the samples or of one or more components thereof isdetected—serially or in a parallel, serial-parallel or hybridparallel-serial manner—at an average sample throughput of not more thanabout 10 minutes per sample. As used in connection herewith, the term“average sample throughput” refers to the sample-number normalized total(cumulative) period of time required to detect a property of two or moresamples with a characterization system. The total, cumulative timeperiod is delineated from the initiation of the characterization processfor the first sample, to the detection of a property of the last sampleor of a component thereof, and includes any intervening between-samplepauses in the process. The sample throughput is more preferably not morethan about 8 minutes per sample, even more preferably not more thanabout 4 minutes per sample and still more preferably not more than about2 minutes per sample. Depending on the quality resolution of thecharacterizing information required, the average sample throughput canbe not more than about 1 minute per sample, and if desired, not morethan about 30 seconds per sample, not more than about 20 seconds persample or not more than about 10 seconds per sample, and in someapplications, not more than about 5 seconds per sample and not more thanabout 1 second per sample. Sample-throughput values of less than 4minutes, less than 2 minutes, less than 1 minute, less than 30 seconds,less than 20 seconds and less than 10 seconds are demonstrated in theexamples. The average sample-throughput preferably ranges from about 10minutes per sample to about 10 seconds per sample, more preferably fromabout 8 minutes per sample to about 10 seconds per sample, even morepreferably from about 4 minutes per sample to about 10 seconds persample and, in some applications, most preferably from about 2 minutesper sample to about 10 seconds per sample.

As for screening throughput for parallel embodiments, up to 96 librarymembers may have their mechanical properties measured simultaneously inabout 10 minutes or less, preferably about 5 minutes or less and evenmore preferably in about 1 minute or less. In some parallel embodiments,screening throughput of even about 30 seconds or less may beaccomplished for an array of the sizes discussed herein, e.g., up to 96samples or members in the array.

A sample-throughput of 10 minutes per sample or less is important for anumber of reasons. Systems that detect a property of a sample or of acomponent thereof at the aforementioned sample throughput rates can beemployed effectively in a combinatorial research program. From acompletely practical point of view, the characterization rates are alsoroughly commensurate with reasonably-scaled polymer sample librarysynthesis rates. It is generally desirable that combinatorial screeningsystems, such as the polymer characterization protocols disclosedherein, operate with roughly the same sample throughput as combinatorialsynthesis protocols—to prevent a backlog of uncharacterizedpolymerization product samples. Hence, because moderate scalepolymer-synthesis systems, such as the Discovery Tools™ PPR-48™ (SymyxTechnologies, Santa Clara Calif.), can readily prepare polymer librarieswith a sample-throughput of about 100 polymer samples per day, ascreening throughput of about 10 minutes per sample or faster isdesirable. Higher throughput synthesis systems demand highercharacterization throughputs. The preferred higher throughput values arealso important with respect to process control applications, to providenear-real time control data.

Additionally, as shown in connection with the examples provided herein,the characterization of polymer samples at such throughputs can offersufficiently rigorous quality of data, to be useful for scientificallymeaningful exploration of the material compositional and/or reactionconditions research space.

Other Screens

The present invention may be employed by itself or in combination withother screening protocols for the analysis of liquids or theirconsitituents. Without limitation, examples of such screening techniquesinclude those addressed in commonly-owned U.S. Pat. Nos. 6,182,499(McFarland, et al); 6,175,409 B1 (Nielsen, et al); 6,157,449 (Hajduk, etal); 6,151,123 (Nielsen); 6,034,775 (McFarland, et al); 5,959,297(Weinberg, et al), 5,776,359 (Schultz, et al.), commonly owned andco-pending U.S. patent application Ser. No. 09/580,024 titled“Instrument for High Throughput Measurement of Material PhysicalProperties and Method of Using Same,” filed on May 26, 2000, all ofwhich are hereby expressly incorporated by reference herein.

Screening techniques may also include (without limitation) opticalscreening, infrared screening, electrochemical screening, flowcharacterization (e.g., gas, liquid or gel-phase chromatography),spectrometry, crystallography, or the like.

It will be appreciated from the above that many alternative embodimentsexist for high throughput mechanical property screening within the scopeof the present invention. Accordingly, the instruments and methodsdiscussed above are to be considered exemplary and nonlimiting as to thescope of the invention.

What is claimed is:
 1. A method for screening an array of materials fora mechanical property, comprising: providing a flexible substrate;depositing a library comprising at least four different material samplesonto said substrate; mounting said substrate onto a mounting member withat least four openings, such that said at least four samples are atleast partially aligned with said at least four openings; applyingpressure with at least one fluid to cause each of said samples todisplace in response to said pressure; and monitoring a response of eachof said samples to said pressure with at least one response sensingdevice.
 2. The method of claim 1, wherein the method is capable ofscreening at least two of said samples of said library simultaneously.3. The method of claim 1, wherein the method is capable of screening atleast twenty-four samples of said library simultaneously.
 4. The methodof claim 1, wherein a screening throughput rate of said library is nogreater than about ten minutes.
 5. The method of claim 1, wherein saidpressure is applied to each of said samples in sequential order and ascreening throughput rate is no greater than 10 minutes per said sample.6. The method of claim 1, wherein said mechanical property is selectedfrom the group consisting of flexure, uniaxial extension, biaxialcompression, shear, stress and strain at failure, toughness, storagemodulus, loss modulus, and mixtures thereof.
 7. The method of claim 1,further comprising regulating environmental conditions of said samples.8. The method of claim 1, wherein said at least one response sensingdevice is selected from the group consisting of an electronic pressuresensor, an optical response sensing device selected from the groupconsisting of optical reflectance, optical interferometry, shadowillumination, and a combination thereof, an electrical response sensingdevice selected from the group consisting of capacitance, resistance,tunneling, electromechanical switching, and a combination thereof, adual pressure sensing device, and a combination thereof.
 9. The methodof claim 1, wherein said samples are mounted on said substrates bymechanically securing, magnetically securing, electromagneticallysecuring, electromechanically securing, chemically securing, or acombination thereof.
 10. The method of claim 1, wherein said pressureapplied by said fluid is created by a source selected from the groupconsisting of a piston in a cylinder, a temperature controller forvarying the temperature of said fluid, a heat transfer device selectedfrom the group consisting of a resistance heater, a liquid-liquid heatexchanger that is connected to a reservoir of exchange fluid, aliquid-gas heat exchanger that is connected to a reservoir of exchangefluid and a combination thereof, and a combination thereof.
 11. Themethod of claim 1, wherein said fluid is chemically inert to saidlibrary of material samples, allows said pressure applied to saidsamples to be controlled and variable, and is selected from the groupconsisting of air, argon, hydrogen, nitrogen, helium, fluorocarbonliquids, ethanol, water, mercury and mixtures thereof.
 12. The method ofclaim 1, wherein at least two fluids are used to apply pressure to oneof said samples, said two fluids being mutually immiscible and whereinseparation between said two fluids is maintained by gravity, surfacetension, or a mixture thereof.
 13. The method of claim 1, wherein saidpressure is a negative pressure.
 14. The method of claim 1, wherein eachof said samples has an area of less than about 100 mm².
 15. The methodof claim 1, wherein each of said sample has a thickness of less thanabout 500 microns.
 16. The method of claim 1, wherein said pressure isselected from the group consisting of monotonic, sinusoidal,discontinuous, and a combination thereof.
 17. A method for screening anarray of materials for a mechanical property, comprising: providing aflexible substrate; depositing a library of at least four differentmaterial samples onto said substrate; measuring the thickness of each ofsaid samples; mounting said substrate onto a mounting member with atleast four openings, such that said at least four samples are at leastpartially aligned with said at least four openings; compressing at leastone transmission fluid against said substrate causing a pressure to beapplied to each of said samples; monitoring a response of each of saidsamples to said compression with at least one response sensing deviceselected from a the group consisting of an electronic pressure sensor,an optical response sensing device, an electrical response sensingdevice, a dual pressure sensing device, and a combination thereof; andranking said samples relative to each other according to theirrespective performance.
 18. The method of claim 17, wherein the methodis capable of screening at least two of said samples of said librarysimultaneously.
 19. The method of claim 17, wherein a screeningthroughput rate of said library is no greater than about ten minutes.20. The method of claim 17, wherein said pressure is applied to each ofsaid samples in sequential order and a screening throughput rate is nogreater than 10 minutes per said sample.
 21. The method of claim 17,wherein said mechanical property is selected from the group consistingof flexure, uniaxial extension, biaxial compression, shear, stress andstrain at failure, toughness, Young's modulus, complex modulus, andmixtures thereof.
 22. The method of claim 17 further comprisingregulating environmental conditions of said samples.
 23. The method ofclaim 17, wherein said samples are mounted on said substrates bymechanically securing, magnetically securing, electromagneticallysecuring, electromechanically securing, chemically securing, or acombination thereof.
 24. The method of claim 17, wherein saidcompression originates from a source selected from the group consistingof a piston in a cylinder, a temperature controller for varying thetemperature of said transmission fluid, a heat transfer device selectedfrom the group consisting of a resistance heater, a liquid-liquid heatexchanger that is connected to a reservoir of exchange fluid, aliquid-gas heat exchanger that is connected to a reservoir of exchangefluid and a combination thereof, and a combination thereof.
 25. Themethod of claim 17, wherein said transmission fluid is chemically inertto said samples, allows said compression to be controlled and variable,and is selected from the group consisting of air, argon, hydrogen,nitrogen, helium, fluorocarbon liquids, ethanol, water, mercury andmixtures thereof.
 26. The method of claim 17, wherein two transmissionfluids are used to apply pressure to one of said samples, wherein saidtwo transmission fluids are mutually immiscible and separation betweensaid two transmission fluids is maintained by gravity, surface tension,or a mixture hereof.
 27. The method of claim 17, wherein each of saidsamples has an area of less than about 100 mm².
 28. The method of claim17 wherein each of said samples has a thickness of less than about 500microns.
 29. A method for screening an array of materials for amechanical property, comprising: providing a mounting member having aplurality of openings, wherein said mounting member is adapted forconnection to a source of a fluid pressure; placing a flexible substratehaving a library of at least two different material samples depositedthereon onto a surface of said mounting member over said openings fordefining a substantially gas tight vessel, wherein each of said sampleshas an area of less than about 100 mm² and a thickness of less than 500microns; aligning said samples with said openings; introducing at leastone fluid that is chemically inert to said samples, and is selected froma the group consisting of air, argon, hydrogen, nitrogen, helium,fluorocarbon liquids, ethanol, water, mercury and mixtures thereof intosaid mounting member for applying pressure to each of said samples;regulating environmental conditions of said samples; using a sourceselected from the group consisting of a piston in a cylinder, atemperature controller for varying the temperature of said transmissionfluid, a heat transfer device selected from the group consisting of aresistance heater, a liquid-liquid heat exchanger that is connected to areservoir of exchange fluid, a liquid-gas heat exchanger that isconnected to a reservoir of exchange fluid and a combination thereof,and a combination thereof, to apply pressure to said substrate andcausing each of said samples to displace in response to said pressure;and monitoring a response of each of said samples to said pressure withat least one response sensing device selected from the group consistingof an electronic pressure sensor, an optical response sensing device, anelectrical response sensing device, a dual pressure sensing device, anda combination thereof, wherein said mechanical property is selected fromthe group consisting of flexure, uniaxial extension, biaxialcompression, shear, stress and strain at failure, toughness, Young'smodulus, complex modulus, and mixtures thereof.
 30. The method of claim29, wherein the method is capable of screening at least two of saidsamples of said library simultaneously.
 31. The method of claim 29,wherein a screening throughput rate of said library is no greater thanabout ten minutes.
 32. The method of claim 29, wherein said pressure isapplied to each of said samples in sequential order and a screeningthroughput rate is no greater than 10 minutes per said sample.
 33. Themethod of claim 29, wherein two fluids are used to apply pressure to oneof said samples, wherein said two fluids are mutually immiscible andseparation between said two fluids is maintained by gravity, surfacetension, or a mixture thereof.